Clinical Trials Register

Summary
EudraCT Number:	2019-003858-85
Sponsor's Protocol Code Number:	HFIRONT
National Competent Authority:	Austria - BASG
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2020-01-17
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Austria - BASG

A.2

EudraCT number

2019-003858-85

A.3

Full title of the trial

Randomized double-blind explorative controlled clinical trial analyzing the effects of ferric carboxymaltose in patients with iron deficiency and chronic heart failure

Randomisierte doppel-blinde explorative kontrollierte klinische Studie welche die Effekte von Eisencarboxymaltose bei Patienten mit Eisenmangel und chronischer Herzinsuffizienz analysiert (HFIRONT)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Effects of iron therapy in patients with chronic heart failure

Effekte von Eisentherapie bei Patienten mit chronischer Herzinsuffizienz

A.3.2

Name or abbreviated title of the trial where available

HFIRONT

A.4.1

Sponsor's protocol code number

HFIRONT

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Medical University Innsbruck
B.1.3.4	Country	Austria
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Medical University Innsbruck
B.4.2	Country	Austria
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Medical University Innsbruck
B.5.2	Functional name of contact point	Department of Internal Medicine II
B.5.3	Address:
B.5.3.1	Street Address	Anichstraße 35
B.5.3.2	Town/ city	Innsbruck
B.5.3.3	Post code	6020
B.5.3.4	Country	Austria
B.5.4	Telephone number	00430512504 23251
B.5.5	Fax number	00430512504 23317
B.5.6	E-mail	guenter.weiss@i-med.ac.at

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Ferinject
D.2.1.1.2	Name of the Marketing Authorisation holder	Vifor France, Paris La D#efense Cedex, Frankreich
D.2.1.2	Country which granted the Marketing Authorisation	Austria
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Ferinject
D.3.4	Pharmaceutical form	Concentrate and solvent for concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	FERRIC CARBOXYMALTOSE
D.3.9.1	CAS number	9007-72-1
D.3.9.2	Current sponsor code	FCM
D.3.9.3	Other descriptive name	Ferric Carboxymaltose
D.3.9.4	EV Substance Code	SUB66620
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

This is a randomized double-blind explorative controlled clinical Trial that analyses the effects of 1000mg ferric carboxymaltose in patients with chronic heart failure and iron deficiency.

Dies ist eine randomisierte doppel-blinde explorative kontrollierte klinische Studie, welche die Effekte von 1000mg Eisencarboxymaltose bei Patienten mit chronischer Herzinsuffizienz und Eisenmangel untersucht

E.1.1.1

Medical condition in easily understood language

Effects of iron therapy in patients with chronic heart failure and iron deficiency.

Effekte von Eisentherapie bei Patienten mit chronischer Herzinsuffizienz und Eisenmangel.

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Primary objective of this study is to identify the mechanism(s) underlying the beneficial effects of iron supplementation in iron-deficient patients with CHF.

E.2.2

Secondary objectives of the trial

Secondary objective is to identify those patients who may benefit from iron supplementation as compared to those who will not. Another aim of this study is to evaluate the therapeutic efficacy based on the underlying cause of iron deficiency (absolute versus functional ID), inflammatory status and co-medications.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Written, signed and dated informed consent.
2. Male and female patients over 18 years.
3. Women of childbearing potential must have a negative pregnancy test and must refrain from breastfeeding. Women who are postmenopausal (1 year since last menstrual cycle), surgically sterilized or who have undergone a hysterectomy are considered not to be of childbearing potential.
4. NYHA class of higher than or equal to NYHA class II
5. Left ventricular ejection fraction (LV-EF) less than or equal to 40% (HFrEF) as assessed by echocardiography, radionuclide ventriculography or contrast angiography within the last 30 days.
6. Iron deficiency (ID) defined as ferritin < 100 μg/L in combination with a transferrin saturation < 20 % (absolute ID) or ferritin 100 – 300 μg/L in combination with a transferrin saturation < 20 % (functional ID)
7. Haemoglobin < 140 g/L

E.4

Principal exclusion criteria

1. Cardiac surgery or coronary angioplasty within 30 days before study drug initiation.
2. Acute coronary syndrome within 30 days before study drug initiation.
3. Patients who are scheduled for cardiac surgery or angioplasty in the next 3 months.
4. Current implanted ventricular assist device (VAD)
5. Stroke or transient ischemic attack (TIA) within 3 months before study drug initiation.
6. Dialysis-dependent renal failure (eGFR < 20 mL/min/1.73m2)
7. Severe Iron deficiency defined as ferritin < 15 μg/L
8. Phosphate levels below the lower limit normal before study drug initiation (< 0.80 mmol/L).
9. Active infection as defined by current use of oral or intravenous antimicrobial agents.
10. Anaemia with known cause other than iron deficiency (ID) or chronic disease.
11. Malignancies
12. Body weight < 50 kg
13. Known allergy against intravenous iron preparation
14. Iron substitution, erythropoietin therapy or blood transfusion in the previous 6 months.
15. Changes in CHF therapy or lipid-lowering therapy within the last 30 days.
16. Participation in another interventional trial.
17. Pregnant woman and nursing mother.

E.5 End points

E.5.1

Primary end point(s)

1. Changes in blood count (including reticulocyte count and reticulocyte hemoglobin content), iron, Tf, TSAT, ferritin, sTfR, hepcidin-25, hsCRP, calprotectin, neopterin, IL-6, IL-10, TNF-��, FACS peripheral, NT-proBNP, troponin T, creatinine (GFR), ASAT, ALAT, AP, GGT, LDH, triglycerides, total cholesterol, LDL, HDL, electrolytes (Na, K, P, Ca), PTH, 1,25-(OH)2 vitamin D and 25-OH vitamin D, LCN2, EPO, ERFE, PDGF-BB, VEGF, FGF23, secretoneurin, TBARS, TOC, OxLDL and metabolites (ATP, NADH/NAD, Lactate, Succinate, Citrate, Pyruvate, free fatty acids), tryptophan, kynurenine, tyrosine and phenylalanine.
2. Changes in blood gases (pH, pCO2, pO2, SaO2, HCO3, BE)
3. Changes in mitochondrial iron and Krebs cycle metabolism gene expression in monocytes detected by RT-PCR.
4. Changes in mitochondrial respiration of selected and randomly assigned patients measured with OROBOS respirometry.
5. Changes in EndoPAT, DVA
6. Changes in pulmonary function detected by spirometry and diffusion measurement
7. Time to death, high-urgent transplantation, ventricular assist device (VAD) implantation or non-fatal HF event requiring i.v. vasoactive therapy (i.v. diuretics, i.v. vasodilators or i.v. inotropes – either in-hospital or ambulatory in an emergency department) or hospitalization for any reason
8. Changes in background medication

E.5.1.1

Timepoint(s) of evaluation of this end point

end of the study

E.5.2

Secondary end point(s)

1) Change in functional status
# 6-minute walk test (6MWT) at baseline, day 2 and day 90
# New York Heart Association (NYHA) class at baseline, day 2 and day 90
# Change in LV-EF from baseline to day 90
2) Change in symptoms
# Kansas City Cardiomyopathy Questionnaire (KCCQ) – clinical summary score – from baseline to day 2 and day 90
# European Quality of Life-5 Dimensions (EQ-5D) – clinical summary score – from baseline to day 2 and day 90
# Difference in Patients Global Assessment (PGA) from baseline to day 2 and day 90

E.5.2.1

Timepoint(s) of evaluation of this end point

end of the study

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

100

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-02-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-12-11

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2021-12-14

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